In the next year, we will continue to explore the biochemical genetics of our control mutants in Neurospora, particularly the nucleocytoplasmic interactions between constitutive mutants and null mutants in heterocaryons and in partial diploids. We will extend our findings that the nuclear membrane provides a barrier for certain regulatory signals between different nuclei in a heterocaryon. We will try to isolate suppressible nonsense mutants at the cys-3 locus to get additional evidence that it normally makes a protein product. We will also try to isolate more mutants in the "phosphorus family" of enzymes, particularly mutants with structurally altered alkaline phosphatase, and mutants that lack the high-pH phosphate permease. Dr. Totten will continue working with the nuclear proteins of Neurospora. In particular, we hope to see changes in some of the nuclear proteins when cultures are grown under different nutritional regimens, and possibly there will be observable changes in the nuclear proteins of some of our regulatory mutants. Dr. Littlewood will attempt to develop a gene-enzyme regulatory system in yeast, comparable to the ones we are studying in Neurospora. Provisionally, she will look at the ATP-dependent urea hydrolase, since it appears to be more highly repressible/inducible than other enzymes that have been observed in yeast. In addition, we will try to select yeast heterocaryons by a scheme she has devised.